The choriocapillaris, Bruch's membrane (BM), and retinal pigment epithelium (RPE) supply the major fraction of nutrients required by the photoreceptors and other cells in the outer neural retina. A knowldege of the fundamental properties of these structures which influence macromolecular movement is vital to the understanding of normal eye function and the pathogenesis of ocular dysfunction due to genetic, age related, and systemic disorders in which they may be involved. We have demonstrated that the choriocapillary endothelium and BM of the rat form a substantial barrier to intravenously administered tracers of different sizes. Hence, these structures may be regarded as "pre-filters" in series with the RPE, a major arm of the blood-retinal barrier. This ultrastructural study will examine some basic characteristics of the choriocapillares, BM, and RPE which are responsible for regulating the movement of molecules bound for the neural retina. These are (1) size restriction due to molecular sieving, (2) retardation due to coulombic interactions of circulating substances with anionic (negative) molecules on the endothelial and RPE surfaces and within BM, (3) interaction of molecules with carbohydrates on the cell surfaces and within BM, and (4) complete restriction by the apicallateral junctions of the RPE. Permeability will be further studied by comparing the luminal and extravascular levels of important plasma proteins which have different sizes. These will be identified by sensitive immunocytochemical methods. Intravascularly injected hemeproteins of discrete sizes but with different molecular charges will be used to examine the size-charge factors associated with the restrictive properties of the eye structures. Their activities will be visualized by cytochemical techniques. With polycationic (positive) probe molecules such as cationic ferritin, the distribution of anionic sites on the choriocapillary sub-structures and basal membranes of the RPE will be ascertained. These will be employed in conjunction with enzymes which cleave specific anionic moieties to establish the chemical nature of these sites. The effects of polycations upon RPE architecture and junctions will also be investigated. Carbohydrate residues on the capillary surface, in BM, and on the basal membranes of the RPE will be marked by lectin affinity cytochemistry. These experiments will establish a baseline for studying ocular changes in animal models of human disease.